Tetranuclear condensation product and process of preparing the same



Patented Dec. 9, 1941 TETRANUCLEAR CONDENSATION PRODUCT AND PROCESSPREPARING THE SAME Walter Salzer and Hans Andersag, Wuppertal-Elberfeld, Germany, assignors to Winthrop Chemical Company, Inc., NewYork, N. Y., a corporation of New York No Drawing. Application May 16,1939, Serial 20 Claims.

This invention relates to new condensation products and to a process ofpreparing the same.

In accordance with the present invention 2 keto 1,2,3,4tetrahydronaphthalenes which contain in the 1-position an alkyl group ora cyclically substituted alkyl group which group contains a reactivehydrogen atom at one of the carbon atoms 3 and 4 numbered from thecarbon atom connected with the naphthalene radical, or substitutionproducts of the compounds specified, can be converted to tricyclic andif the compounds contain the cyclically substituted alkyl group totetracyclic condensation products when subjecting the said startingproducts to intramolecular condensation by means of aringclosing-condensing agent. Such ringclosing-condensing agents arepreferably highly concentrated sulfuric acid, for instance 98%concentrated sulfuric acid or 80% sulfuric acid which latter may be usedtogether with an indifferent solvent, such as benzene; another suitablecondensing agent is for instance phosphorus oxychloride. Thecondensation temperature is adapted to the particular condensing agent;when working with concentrated sulfuric acid the condensation isadvantageously carried out at a temperature of to C., when using 80%sulfuric acid a temperature of 70 to 80 C. has proved suitable, whenusing phosphorus oxychloride short gentle heating is advisable. Thus,for instance, phenanthrene and benzoindene derivatives may be obtained;when using 2-keto- 1,2,3,4=-tetrahydronaphthalenes containing in the1-position a phenylmethyl or substituted phenylmethyl group,benzofluorene compounds are obtained; chrysene compounds are formed whensubjecting 2-keto-1,2,3,4-tetrahydronaphthalenes which contain in thel-position a phenylethyl or substituted phenylethyl radical to thecondensa tion.

The course of the reaction is most surprizing in View of the known fact,that the 2-keto- 12,3,4-tetrahydronaphthalene has a great tendency toaromatization; it is for instance converted into naphthalene even onheating it to boiling while splitting off water.

The products thus obtainable are intended to be used for pharmaceuticpurposes, if desired after further transformation of the substituentspresent. The condensation products containing alkoxy substituents, suchas the methoxy and ethoxy group show particularly after splitting offthe alkyl groups of the alkoxy substituents oestrus activity.

In Germany May 17, 1938 obtainable by reacting upon a 2-keto-l,2,3,4-tetrahydronaphthalene in the presence of a strongly alkaline condensingagent and of a solvent which is inert to the starting materials with aphenyl-alkyl-halide.

The invention is illustrated by the following examples without beingrestricted thereto, the parts being by weight:

1 gram of l-(beta-phenylethyl) -2-keto-l,2,3,4- tetrahydronaphthalene istreated with 5 cos. of concentrated sulfuric acid at 0 to 10 C. After 5minutes the reaction mixture is poured on to ice and the precipitatedsolid substance is dissolved in ether. Crystals of'the5,6,11,12-tetrahydrochrysene (numbering comp. Annalen der Chemie 311,page 257) melting at 105 C. are obtained. The reaction proceedsaccording to the following reaction scheme:

In an analogous manner the 3-methoxy- 5,6,11,12-tetrahydrochrysene ofthe formula:

O CHa H2 is obtained from alcohol in crystals melting at 91 C. from thel-(beta-phenylethyl) -6-methoxy 2-keto 1, 2, 3, 4 tetrahydronaphthalenethe l,2-benzo-3,4-dihydro-5- (or 7-) -methoxyfluoren of the formula:

melting at 122 C. (from alcohol) is obtained from the1-(3-methoxybenzyl)-2-keto-1,2,3,4-

The starting materials above specified are tetrahydronap t a ne. Thecorresponding Ph it causes full oestrus even in' small doses noliccompound, the 1,2-benzo-3,4-dihydro-5- (or 7-)-hydroxyfiuoren, isobtained by demethylating the methoxy compound by treatment with excessmethyl magnesium iodide at 200 C.; it has a strong oestrus activity onthe castrated female rat; crystals of the 3-methoxy-'5;6,11;12-tetrahydrochrysene melting at 163 C. (from benzene) containing a furthermethoxy-group in 7- or 9position and having in the latter case theformula:

are obtained from 1-(beta-3'-metho iyphenyl-' ethyD-fi-met'hoxy- 2ketop- 1,2,3,4 tetrahydrobridge selected from the class consisting of''CH2- and -'CH2CH2+ with a benzene ring and the 2-po'sition of the3,4-dihydr'onaphthalene is directly connected with the "benzene ring inortho-position to said bridge. 7

2. 5,6,11,12 tetrahydrochrysenes.

3. 5,6.11,12-tetrahydrochrysenes which are substituted by substituentsof the group consisting of hydroxy and methoxy groups.

4. 5,6,11,lz-tetrahydrochrysenes which are substituted :in 3-pos'i'tionand in one of the positions 7 and 9 "by s'ubstituents of thegroupconsisting of hydroxy and methoxy groups.

5. 1,2-benzo 3.4-dihydro-fiuorenes.'

substituted by substituents of the group consisting of hydroxy and'methoxy groups.

7. 1,2benzo-3,4 dihydr0-flu0renes which are substituted in one-of thepositions 5 and 7 by a substituent ofthegroup consisting of hydroxy andmethoxy groups.

8. The process which comprises subjecting aZ-keto-1,2,3,4-tetrahydronaphthalene which is substituted in l-positionby a phenylalkyl radical substituted in l-position by a phenylethylradical having a reactive hydrogen atom at the phenyl radical inortho-posi-tion to the ethyl "radical, to

.intramolecular condensation by means of a ringclosing-condensing agent.

10. The'process which comprises subjecting a which is substituted inl-position by a phenylethyl radical -having a reactive hydrogen atom atitheph'enyl .iadial fin ortho-position to the ethyl radical,to-intramolecular condensation by means ofja ring-closing-condensingagent.

having a hydrogen atom'at'the phenylradical in' ortho-position:to thealkyl radical to .i'ntrae 11. The process which comprises subjecting1--phenylethyl- 2-keto-1,2,3,4 tetrahydro 6 alkoxy naphthalene tointramolecular condensation by means of a ringclosing-condensing agent.

-1 2'. The process which comprises subjecting l tbeta ii'alkoxyphenylthyl) e km ($12,351- "tetra-hydrm6alkoxy+naphthalene *t'o--intramole- 'c-ular condensation by means of a "rin'gclosingcondensingagent.

13. The process which comprises subjecting *l- "naphth'alene tointramolecular condensation by 'meansiof highly concentrated sulfuricacid.

14. The process which comprises subiectin l-phehylethyl 2 k elfo- 1,2 14ttifhydib 6 'methoxynaphthalene t'o intramoiecular condensation by meansof highly concentrated acid.

1-5. The processwhich comprises subjecting'l'-(b'eta-3'=a;lkoxyphenylethyl) 2 ken)"- 1, 2,???- tetra-hydro fialkoxy naphthalene to im -smote 'cu'lar condensa'tion by means of highlycommtrafted sulfuric "acid.

16; 3+ hydroXy'- 5,6 51 1,12 tetrahydrochrysenes which jaresubstitutedone of. the positions "7 fand19 *by a hydl'flkyliglbllp. I

17. 1,2=b enzo-3,4=dihydrdfiuorenes which are substituted 'in'one of thepositions 5 and 7 by a y oxy f r up. 1 1 V naphthalene toint'ramolecular condensation by v means of a 'ringolosingcondensing"agent.

19."."Ihe processwhi'ch comprises "subjecting a 1- 3' "-alkoxybenz'y1-2-keto f1j2',3 -,'4 tetrahydronaphthalene to intramolecuiar condensationby means ofhighly conc ntrated sul furi'c'acid. v .zdf'rne process whichcom ris s subjecting 1-(3" methoxybenzyl=)' z-icfio iflj3g i tetrahydronaphthalenefto "intrarnolecuiar condensation by means orhighly-concentrated sulfuric acid.

HANS. ANDERSAG.

